Cetewayo Rashid
University of Kentucky, KY·Pharmacology
Flame retardants are added to furniture and other household goods to meet flammability rules, but some escape into indoor dust and end up inside people. One of them, the organophosphate flame retardant TDCPP (tris(1,3-dichloro-2-propyl) phosphate), is swallowed mainly through hand-to-mouth contact and broken down in the body to a chemical called BDCPP, which is detectable in the urine of about 90% of Americans.
- Fields
Pharmacology
Physiology
Public Health & Epidemiology
- Topics
flame retardants
organophosphate esters
endocrine disrupting chemicals
- Grants
- 1 known grant, through Jun 2029
What they work on
- Test whether activation of PXR, a nuclear receptor that senses foreign chemicals, drives liver-specific insulin resistance in male mice fed diets containing the flame retardant TDCPP, using mice engineered to carry the human PXR gene.
- Determine whether PXR activation is required for metabolic disruption by comparing PXR-deficient mice and dietary exposure to BDCPP, the TDCPP breakdown product that does not activate PXR.
- Assess insulin action and insulin signaling directly in livers of male and female humanized PXR mice, using euglycemic clamp measurements and body composition analysis.
- Establish whether sex hormones underlie the male-specific effect by gonadectomizing male and female mice before TDCPP exposure and tracking body fat and glucose handling.
- Map the gene programs behind the sex difference by messenger RNA sequencing of livers from humanized PXR, PXR-deficient, and castrated mice exposed to TDCPP.
More about the research
National survey data tie higher urinary BDCPP to metabolic syndrome, a cluster of conditions including abdominal fat gain and high blood sugar, and the association shows up only in men. This project asks how a widespread indoor contaminant could disturb metabolism in males while females appear protected.
Why it matters
Nearly everyone in the U.S. carries traces of this flame retardant, and in men exposure tracks with metabolic syndrome, a precursor to type 2 diabetes. Pinpointing the receptor and hormonal steps involved could support screening strategies for flame retardants that meet fire-safety rules without disturbing metabolism, and may help explain why many hormone-disrupting chemicals affect men and women differently.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michele Marcus
Emory University, GA·Public Health & Epidemiology
Determine whether cancer incidence and mortality are higher in the Michigan PBB Registry than in the general U.S. population, using standardized incidence and mortality ratios from linked death and state cancer registry data.
Tiangang Li
University of Oklahoma-Health Sciences Center, OK·Physiology
Identify which Cullin-RING E3 ligase complex mediates the benefits of neddylation inhibitors on blood sugar and liver fat, using liver-specific knockout mice and AAV8 gene delivery in mouse models of fatty liver disease.
Shelley Tischkau
Southern Illinois University-Carbondale, IL·Physiology
Test whether restricted feeding, limiting food intake to set times of day, can reset circadian clock function and restore adipose tissue rhythms after the clock is disrupted by chronic activation of the aryl hydrocarbon receptor (AhR) by pollutants such as dioxins.
The school
University of Kentucky: 34 labs on PI Pages, $528M a year on research, 319 research doctorates a year.
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